This invention relates to novel 3-[2-hydroxy-4-(substituted)phenyl]-4(or 5-)-substituted)cycloalkanones and cycloalkanols useful as analgesic agents and as anti-emetic agents; to derivatives thereof, intermediates therefore and processes for their preparation.
Despite the current availability of a number of analgesic agents, the search for new and improved agents useful for the control of broad levels of pain and accompanied by a minimum of side-effects continues. The most commonly used agent, aspirin, is of no practical value for the control of severe pain and is known to exhibit various undesirable side-effects. Other analgesic agents, such as meperidine, codeine, and morphine, possess addictive liability. The need for improved and potent analgesic agents is, therefore, evident.
Compounds having utility as analgesics, tranquilizers, sedatives, antianxiety agents and/or as anticonvulsants, diuretics and antidiarrheal agents are described in Belgian Patents Nos. 870,404 and 870,402, both granted Mar. 12, 1979. Belgian Patent No. 870,404 describes 3-[2-hydroxy-4-(substituted)phenyl]cycloalkanones and cycloalkanols which may have at the 4-position of the cycloalkanone or cycloalkanol residue, an alkyl, alkenyl, phenyl or phenylalkyl substituent; or, at the 5-position, an alkyl substituent, and Belgian Patent No. 870,402 discloses certain 2-(acyclic substituted)phenols; namely, 2-(hydroxyalkyl)-4-(substituted)phenols and 2-(oxoalkyl)-4-(substituted)phenols.
U.S. Pat. No. 3,576,887, issued Apr. 27, 1971, discloses a series of 1-(1'-hydroxy)alkyl-2-(o-hdroxyphenyl)cyclohexanes which exhibit central nervous system depressant properties.
Our concurrently filed application, Ser. No. 189,402, filed Sept. 19, 1980, now U.S. Pat. No. 4,285,867, issued Aug. 25, 1981, entitled "Pharmacologically Active 4-[2-Hydroxy-4-(Substituted)phenyl]Naphthalen-2(1H)-ones and 2-ols, Derivatives Thereof and Intermediates Therefore," describes a series of 4-[2-hydroxy-4-(substituted)phenyl]naphthalen-2(1H)-ones and 2-ols useful as CNS agents and as antiemetic agents.
U.S. Pat. No. 3,974,157 describes 2-phenylcyclohexanones which can be substituted in the phenyl ring with up to two alkyl, hydroxy or alkoxy groups as intermediates for preparation of 1-(aminoalkyl)-2-phenylcyclohexanols useful as analgesics, local anesthetics and antiarrhythmics.
Chemical Abstracts 85, 176952f (1976) discloses a number of 3-phenyl- and 3-phenylalkylcyclohexanones as intermediates for 2-aminomethyl-3-phenyl (or phenylalkyl)cyclohexanones which exhibit analgesic, sedative, antidepressant and anticonvulsant activities.